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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/F1427    most recent 90599.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ditting, T. Articles by Veelken, R. PubMed PubMed Citation Articles by Ditting, T. Articles by Veelken, R.

Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney?

¹Department of Internal Medicine 4, Nephrology, and Hypertension, ; Departments of ³Physiology and ; ⁴Anatomy, University of Erlangen, Nuremberg; and ; ²Division of Experimental Immunology and Hepatology, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Submitted October 10, 2008 ; accepted in final form August 14, 2009

Peptidergic afferent renal nerves (PARN) have been linked to kidney damage in hypertension and nephritis. Neither the receptors nor the signals controlling local release of neurokinines [calcitonin gene-related peptide (CGRP) and substance P (SP)] and signal transmission to the brain are well-understood. We tested the hypothesis that PARN, compared with nonrenal afferents (Non-RN), are more sensitive to acidic stimulation via transient receptor potential vanilloid type 1 (TRPV1) channels and exhibit a distinctive firing pattern. PARN were distinguished from Non-RN by fluorescent labeling (DiI) and studied by in vitro patch-clamp techniques in dorsal root ganglion neurons (DRG; T11-L2). Acid-induced currents or firing due to current injection or acidic superfusion were studied in 252 neurons, harvested from 12 Sprague-Dawley rats. PARN showed higher acid-induced currents than Non-RN (transient: 15.9 ± 5.1 vs. 0.4 ± 0.2* pA/pF at pH 6; sustained: 20.0 ± 4.5 vs. 6.2 ± 1.2* pA/pF at pH 5; *P < 0.05). The TRPV1 antagonist capsazepine inhibited sustained, amiloride-transient currents. Forty-eight percent of PARN were classified as tonic neurons (TN = sustained firing during current injection), and 52% were phasic (PN = transient firing). Non-RN were rarely tonic (15%), but more frequently phasic (85%), than PARN (P < 0.001). TN were more frequently acid-sensitive than PN (50–70 vs. 2–20%, P < 0.01). Furthermore, renal PN were more frequently acid-sensitive than nonrenal PN (20 vs. 2%, P < 0.01). Confocal microscopy revealed innervation of renal vessels, tubules, and glomeruli by CGRP- and partly SP-positive fibers coexpressing TRPV1. Our data show that PARN are represented by a very distinct population of small-to-medium sized DRG neurons exhibiting more frequently tonic firing and TRPV1-mediated acid sensitivity. These very distinct DRG neurons might play a pivotal role in renal physiology and disease.

classification of neurons; capacitance; TRPV1 channels; ASIC; renal afferent nerve; rat